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Clonal selection theory


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Clonal selection theory

  1. 1. Y. Prvaeen Kumar Msc.Clinical Biochemistry
  2. 2. Other theory's • Side chain theory • Direct template theory • Indirect template theory • Natural selection theory
  3. 3. Side chain theory • Ehrlich (1900) • Cells have surface receptors which have capability to react with substances having complementary side chains • This theory is abandoned when Landsteiner explained Antibodies could be formed against not only natural antigens but also against various synthetic chemicals (riboflavin, estradiol & L- thyroxine)
  4. 4. Direct template theory • Breinl & haurowitz • Alexander • Mudd • The antigen enters antibody forming cells and acts as a template so that antibodies are formed with complimentary combining sites to antigen • Pauling 1940 specificity was determined by folding of the antibody to form tertiary structure fitting antigen molecule
  5. 5. Indirect template theory • Burnet fenner 1949 • A genocopy of antigenic determinant was in corporated in antibody producing cell genome and transmitted to progeny cells
  6. 6. Natural selection theory • Jerne 1955 • Million globulin molecules are formed in embryonic life with full range of antigenic specificities ( natural antibodies) • Antigen when enters it combines with nearly matching • This move on to the antibody producing cells they get activated and produce same kind of antibody
  7. 7. What clonal selection explains..? • It explains how the cells of immune system will react with a specific antigen that enters body
  8. 8. Who introduced it..? • Australian doctor Frank Macfarlane Burnet in 1957 • Widely accepted model
  9. 9. Postulates 1. Each lymphocyte bears a single type of receptor with a unique specificity (by V(D)J recombination). 2. Receptor occupation is required for cell activation. 3. The clone cells derived from an activated lymphocyte will bear receptors of identical specificity as the parental cell. 4. Forbidden cells will be deleted at an early stage.
  10. 10. Primary responseFirst exposure to a foreign antigen, a lag phase occurs in which no antibody is produced, but activated B cells are differentiating into plasma cells. (The lag phase can be as short as 2-3 days, but often is longer, sometimes as long as weeks or months.) • The amount of antibody produced is usually low. • Antibody level declines to the point where it may be undetectable. • The first antibody produced is mainly IgM (although small amounts of Ig G are usually also produced).
  11. 11. Secondary Response • second dose of the same antigen is given days or even years later, an accelerated immune response (IR) occurs. (This lag phase is usually very short (e.g. 3 or 4 days) due to the presence of memory cells.) • The amount of antibody produced rises to a high level. • Antibody level tends to remain high for longer. • The main type of antibody produced is IgG (although small amounts of IgM are sometimes produced).
  12. 12. Cell mediated immune response cellular immunity T-cell immunity many cells • Lymphocytes • Macrophages • Nk cells • No anti body's
  13. 13. Antigen presenting cells • This induces the invaded microorganism to release the antigenic materials…& this antigenic material is presented to T-cells • Types 1. Macrophages (major role) present in all lymphoid tissues 2. Dendritic cells a) Dendritic cells of spleen( filter blood) b) Follicular dendritic cells lymph node (trapping ag) c) Langerhans dendritic cells in skin (traps skin contact organisms  B-lymphocytes antigen receiving & presenting
  14. 14. Entry of micro organism Phagocytosis or APC Antigen is digested into peptides Digested peptide binds with HLA in class II MHC molecule present on APC TCR on T-cell recognizes the antigen and T-cell activated Activated T-cell proliferates Enters circulation interleukin also released from macrophages
  15. 15. T-cells types & role • Helper T-cells (CD4) TH1…IL-2 activates other t cells and gamma interferon it increases the phagocytic activity TH2…IL4 & 5 B-cell activation, proliferation of plasma cells, & antibodies by plasma cell • Cytotoxic T-cells (CD8)(killer T-cells) Releases cytotoxic substances (lysosomal enzymes) Destroys own body tissue affected by foreign bodies • Suppressor T-cells (regulatory T-cells) Suppress the activity of T-cells (CD8 & CD4) • Memory T-cells Not enters circulation remains in tissue.
  16. 16. Humoral immune response Antibody mediated immunity B-cell immunity • Antibodies are secreted into body fluids (blood & lymph) • Humours (Latin) = fluid • It is the major defense mechanism againest bacterial infection
  17. 17. Entry of micro organism Phagocytosis or APC Antigen is digested into peptides Digested peptide binds with HLA in class II MHC molecule present on APC BCR on B-cell recognizes the antigen and B cell activated B-cell proliferation Plasma cells memory cells interleukin also released from macrophages
  18. 18. • Plasma cells  2000 antibodies/sec (immunoglobulins) • Memory cells  present in all lymph nodes in in-active form until the body is exposed with same antigen second exposure to same antigen results in rapid production of antibodies…. ( This is the principle in vaccination)
  19. 19. Reference